Marburg virus glycoprotein mRNA vaccine is more protective than a virus-like particle-forming mRNA vaccine

Area of Science:

• Virology
• Vaccinology
• Immunology

Background:

• Virus-like particle (VLP) vaccines are effective, but their advantages over envelope protein-only vaccines, particularly mRNA-encoded VLPs, require clarification.
• Marburg virus (MARV) poses a significant public health threat, necessitating effective vaccine strategies.

Purpose of the Study:

• To compare the immunogenicity and protective efficacy of mRNA vaccines encoding MARV full-length glycoprotein (GP) delivered alone versus as a VLP.
• To elucidate the immune responses and protective mechanisms elicited by different mRNA vaccine platforms against MARV.

Main Methods:

• Side-by-side comparison of mRNA vaccines encoding MARV GP alone or co-expressing GP and matrix protein VP40 for VLP formation in guinea pigs and mice.
• Assessment of humoral responses, protective efficacy at varying doses, T cell responses (CD4+ and CD8+), and host gene expression (RNA-Seq) in vaccinated animals.
• Electron microscopy was used to confirm VLP formation.

Main Results:

• Both GP-only and VLP mRNA vaccines conferred full protection at the highest dose in guinea pigs, with VLP eliciting a slightly lower humoral response.
• At low doses, GP-only mRNA achieved 100% protection, while VLP mRNA provided only partial protection.
• GP-only mRNA favored CD4+ T cell responses in mice, whereas VLP mRNA induced CD8+ T cell responses.
• VLP mRNA downregulated NF-κB signaling and other pathways, while GP-only mRNA upregulated IFN signaling in guinea pigs.

Conclusions:

• GP-only mRNA vaccines are more immunogenic and protective than VLP mRNA vaccines against Marburg virus, particularly at lower doses.
• The GP-only mRNA vaccine demonstrated robust protection at a dose as low as 1 μg in guinea pigs.
• Differential immune signaling pathways (NF-κB vs. IFN) are modulated by VLP and GP-only mRNA vaccines, influencing protective outcomes.